Acute cardiac disorders including acute coronary syndromes (ACS) encompass a wide spectrum of cardiac ischemic events ranging from unstable angina through to acute myocardial infarction (AMI). AMI presents as the most serious of these events and therefore requires rapid and accurate diagnosis. Patients who present with two or more of the described features (a history of ischemic chest discomfort, evolutionary changes on serial electrocardiogram (ECG) traces and a rise and fall in plasma cardiac biomarkers) are clearly identified as undergoing AMI.1 However, a significant proportion of patients (40%-50%) who present with suspected AMI do not have serial changes on ECG, or typical symptoms thus placing heavy emphasis on circulating biomarker concentrations for accurate diagnosis.2-4 
Accurate early diagnosis of myocardial infarction facilitates prompt introduction of reperfusion treatment, including effective percutaneous or thrombolytic revascularisation and adjunctive anticoagulant and anti-platelet therapy. Such treatments are progressively less effective at reducing mortality and morbidity with each hour of delay in diagnosis and management.2-4 Given the need for accelerated decision-making in this clinical situation, there is considerable interest in the identification of circulating biomarkers providing an early and specific diagnosis of acute cardiac disorders, particularly AMI.
A number of biomarkers have been proposed for this purpose, including creatine kinase-MB (CK-MB), troponin T (TnT), troponin I (TnI) and myoglobin, but there are limitations to their use. Time to detectable or abnormal elevation of plasma cardiac biomarkers can be 6 hours (myoglobin, CK-MB) to 12 hours (TnT, TnI) with peak levels not occurring until 24-48 hours after onset of injury, imposing a window of delay upon precise diagnosis and treatment.1-4 Furthermore, both myoglobin and CK-MB are non-specific and can be secreted from extra-cardiac sources, especially during trauma or surgery.1 Other biomarkers useful for this purpose are BNP (preproBNP 103-134) and N-BNP (preproBNP (27-134) which is also known as NT-proBNP (see FIG. 1). Both peptides are secreted into the circulation.
Measurement of plasma concentrations of BNP and N-BNP early post-AMI has powerful prognostic value2,6,7 and incorporation of plasma concentrations of these peptides into treatment regimes can significantly improve clinical outcomes of patients with heart failure.8 This is particularly true of N-BNP which has a half-life some 14-fold longer than BNP5 and thus provides additional important information regarding long term cardiac performance after AMI.
As with the cardiac biomarkers above, BNP and N-BNP may not reach detectable or abnormal levels for 6 to 12 hours after onset of injury, with peak levels not occurring until 24 to 48 hours after onset. The long term diagnostic/predictive powers of BNP and N-BNP therefore lack the accompanying power of a specific marker providing early specific diagnosis of acute cardiac disorders such as acute cardiac injury within the first few hours of clinical presentation. A need thereof exists for such an early marker.
More recently, it has been suggested that BNP-SP may be useful in diagnosing heart disease (US 2005/0244904, WO 2005/052593). It is generally indicated that levels of BNP-SP will be higher in heart failure patients than normal patients. No time course information as to when to measure BNP-SP levels is provided. It is stated that BNP-SP levels are elevated in conjunction with N-BNP.
It is an object of the present invention to go some way towards fulfilling the need for an early marker of acute cardiac disorders, and/or to at least provide the public with a useful choice.